The long term objective of this project is to investigate the mechanisms governing the regulation of experimental autoimmune encephalomyelitis (EAE). Acute EAE in the Lewis rat is a highly reproducible disease with a predictable course. It serves as a laboratory model for multiple sclerosis and may provide insight into the mechanisms underlying immunopathological responses within the central nervous system. Lewis rats spontaneously recover from EAE, and we have shown that recovery is associated with the appearance of suppressor cells (Ts). These Ts inhibit the activity of the effector T cells (Te) that mediate EAE by downregulating lymphokine production by the Te. The present application proposes to further test our working hypothesis that Ts are induced in response to Te and inhibit the activity of the Te via the production of immunoregulatory lymphokines. The specific aims are: 1. To continue studies of Ts in vitro in order to more fully ascertain the spectrum of immunoregulatory lymphokines produced by these cells. We have reported that transforming growth factor-beta is produced by Ts;this lymphokine downregulates the production of interferon-gamma by Te. 2. To identify the antigenic epitopes that stimulate and activate Ts. We will test the hypothesis that Ts recognize and respond to idiotypic determinants on the T cell receptors (TCR) of the Te. 3. To ascertain the role of B cells and specific antibodies in recovery from EAE. We will investigate whether B cells and antibodies reactive with myelin basic protein antigen and/or effector cell TCR idiotype are produced. 4. To correlate these in vitro findings with in vivo events in order to identify the lymphocyte subpopulations that are required to suppress EAE in rats, and clarify the mechanism by which they function to regulate this autoimmune disease. Immunoregulatory defects attributable to suppressor cells have also been reported in multiple sclerosis. Thus, elucidation of the mechanism of recovery from EAE may advance our understanding of the remission phase of MS.